CHLOROQUINE-INDUCED ACCUMULATION OF GANGLIOSIDES AND PHOSPHOLIPIDS IN SKELETAL-MUSCLES - QUANTITATIVE-DETERMINATION AND CHARACTERIZATION OF STORED LIPIDS

High doses of the lysosomotropic drug chloroquine result in lipid storage in many organs in animals. Miniature pigs, type Coettingen, were used to study the lipid accumulation in skeletal muscle after chloroquine intoxication for > 200 days. The lipids of the quadriceps muscle in intoxicated and in age-matched control pigs were characterized and determined. The lipid storage was larger in skeletal muscle than in any other organ of the intoxicated pigs. The concentration of phospholipids was increased 3-fold, acidic phospholipids relatively more than neutral ones. The lysosome-specific acidic phospholipid bis(monoacylglyceryl)phosphate content was .apprx. 50-fold larger in the intoxicated pigs than in the controls. Cholesterol was increased slightly more than the phospholipids, but there was no particular accumulation of cholesteryl esters, which was shown to occur in the liver. For the 1st time a storage of gangliosides, relatively more pronounced than of other lipids, was demonstrated in skeletal muscle in drug-induced lipidosis. The concentration of total gangliosides was increased 10 to 15-fold, and the pattern of gangliosides showed some distinct changes resulting in at least a 100-fold increase in the concentration of ganglioside GM2 (II3NeuAc-GgOse4Cer).